Correlation between glycated hemoglobin A1c, urinary microalbumin, urinary creatinine, ß2 microglobulin, retinol binding protein and diabetic retinopathy.

BACKGROUND: Retinopathy is the most common microvascular disease of type 2 diabetes, and seriously threatens the life, health and quality of life of patients. It is worth noting that the development of diabetic retinopathy (DR) can be hidden, with few symptoms. Therefore, the preliminary screening of diabetic patients should identify DR as soon as possible, delay disease progression, and play a vital role in its diagnosis and treatment. AIM: To investigate the correlation between glycated hemoglobin A1c (HbA1c), urinary microalbumin (U-mALB), urinary creatinine (U-CR), mALB/U-CR ratio, ß2 microglobulin (ß2MG), retinol binding protein (RBP) and DR. METHODS: A total of 180 patients with type 2 diabetes mellitus attending the Second People's Hospital of Hefei from January 2022 to August 2022 were retrospectively enrolled by ophthalmologists. Based on whether they had combined retinopathy and its degree, 68 patients with diabetes mellitus without retinopathy (NDR) were assigned to the NDR group, 54 patients with non-proliferative DR (NPDR) to the NPDR group, and 58 patients with proliferative DR to the PDR group. General data, and HbA1c, mALB, ß2MG, RBP, mALB/U-CR and U-CR results were collected from the patients and compared among the groups. Pearson's correlation method was used to analyze the correlation between HbA1c, mALB, ß2MG, RBP, mALB/U-CR and U-CR indices, and multiple linear regression was applied to identify the risk factors for DR. Receiver operator characteristic (ROC) curves were also drawn. RESULTS: The differences in age, gender, systolic and diastolic blood pressure between the groups were not statistically significantly (P > 0.05), but the difference in disease duration was statistically significant (P < 0.05). The differences in fasting blood glucose, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, and triglyceride between the groups were not statistically significant (P > 0.05). HbA1c in the PDR group was higher than that in the NPDR and NDR groups (P < 0.05). The levels of mALB, ß2MG, RBP, mALB/U-CR and U-CR in the PDR group were higher than those in the NPDR and NDR groups (P < 0.05). Multiple linear regression analysis showed that disease duration, HbA1c, mALB, ß2MG, RBP, mALB/U-CR and U-CR were risk factors for the development of DR. The ROC curve showed that the area under the curve (AUC) for the combination of indices (HbA1c + mALB + mALB/U-CR + U-CR + ß2MG + RBP) was 0.958, with a sensitivity of 94.83% and specificity of 96.72%, which was higher than the AUC for single index prediction (P < 0.05). CONCLUSION: HbA1c, mALB, mALB/U-CR, U-CR, ß2MG and RBP can reflect the development of DR and are risk factors affecting PDR, and the combination of these six indices has predictive value for PDR.

αB-crystallin/HSPB2 is critical for hyperactive mTOR-induced cardiomyopathy.

Even though aberrant mechanistic target of rapamycin (mTOR) signaling is known to cause cardiomyopathy, its underlying mechanism remains poorly understood. Because augmentation of αB-crystallin and hspB2 was presented in the cortical tubers and lymphangioleiomyomatosis of tuberous sclerosis complex patients, we deciphered the role of αB-crystallin and its adjacent duplicate gene, hspB2, in hyperactive mTOR-induced cardiomyopathy. Cardiac Tsc1 deletion (T1-hKO) caused mouse mTOR activation and cardiomyopathy. Overexpression of αB-crystallin and hspB2 was presented in the hearts of these mice. Knockout of αB-crystallin/hspB2 reversed deficient Tsc1-mediated fetal gene expression, mTOR activation, mitochondrial damage, cardiomyocyte vacuolar degeneration, cardiomyocyte size, and fibrosis of T1-hKO mice. These cardiac-Tsc1; αB-crystallin; hspB2 triple knockout (tKO) mice had improved cardiac function, smaller heart weight to body weight ratio, and reduced lethality compared with T1-hKO mice. Even though activated mTOR suppressed autophagy in T1-hKO mice, ablation of αB-crystallin and hspB2 failed to restore autophagy in tKO mice. mTOR inhibitors suppressed αB-crystallin expression in T1-hKO mice and rat cardiomyocyte line H9C2. Starvation of H9C2 cells activated autophagy and suppressed αB-crystallin expression. Since inhibition of autophagy restored αB-crystallin expression in starved H9C2 cells, autophagy is a negative regulator of αB-crystallin expression. mTOR thus stimulates αB-crystallin expression through suppression of autophagy. In conclusion, αB-crystallin and hspB2 play a pivotal role in Tsc1 knockout-related cardiomyopathy and are therapeutic targets of hyperactive mTOR-associated cardiomyopathy.

Apelin-13 deficiency alters cortical bone geometry, organic bone matrix, and inhibits Wnt/ß-catenin signaling.

Adipokines play key roles in the regulation of obesity, type 2 diabetes mellitus, and bone growth. As a newly discovered hormone in the adipokines family, the precise role of Apelin-13 on bone metabolism is not yet clear. Apelin-13 and 25(OH)D3 expression were detected in freshly isolated serum of healthy individuals and osteoporosis patients with ELISA method. Apelin-13 deficient mice were set up and cortical bone geometry was measured with micro-computed tomography (Micro-CT) at 5 months old, then profile of organic bone matrix genes was detected with quantitative Real-Time PCR (qRT-PCR). Wnt/ß-catenin signaling molecules were assayed in primary osteocytes isolated from neonatal calvarias. Apelin-13 and 25(OH)D3 showed decreased expression in osteoporosis patients. Five-month-old Apelin deficient mice exhibited decreased total and bone marrow cavity area and periosteal and endocortical bone surface. Deficiency of Apelin-13 downregulated collagen maturation associated genes (loxl3 and loxl4) and Wnt/ß-catenin signaling, while loxl2 was upregulated, all of which indicated that Apelin-13 could play a role in regulating skeletal homeostasis. The decrease in bone formation in Apelin-13 deficient mice is associated with downregulation of organic bone matrix genes and Wnt/ß-catenin signaling molecules, all of these indicate that association of Apelin-13 with bone mineral density (BMD) could be mediated by Wnt/ß-catenin pathway.

Contrast-induced nephropathy in patients with diabetes mellitus between iso- and low-osmolar contrast media: A meta-analysis of full-text prospective, randomized controlled trials.

PURPOSE: This study was conducted to compare iso-osmolar contrast medium, iodixanol, with low-osmolar contrast media (LOCM) for assessing contrast-induced nephropathy (CIN) incidence, exclusively in the diabetic population. METHOD: A systematic search was conducted for full-text, prospective, randomized controlled trials (RCTs). The primary outcome was incidence of CIN. Medline, Cochrane Central Register of Controlled Trials, and other sources were searched until May 31, 2017. RESULTS: Twelve RCTs finally met the search criteria. Iodixanol did not significantly reduce the risk of CIN (risk ratio [RR]: 0.72, 95% confidence interval (CI): [0.49, 1.04], p = 0.08). However, there was significantly reduced risk of CIN when iodixanol was compared to a LOCM agent iohexol (RR: 0.32, 95% CI [0.12, 0.89]). There were no differences between iodixanol and the other non-iohexol LOCM (RR: 0.92, 95% CI [0.68, 1.25]). CONCLUSION: In diabetic populations, iodixanol is not associated with a significant reduction of CIN risk. Iodixanol is associated with a reduced risk of CIN compared with iohexol, whereas no significant difference between iodixanol and other LOCM could be found.

Wild-type p53-induced Phosphatase 1 Deficiency Exacerbates Myocardial Infarction-induced Ischemic Injury.

BACKGROUND: Myocardial infarction (MI) is a major disease burden. Wild-type p53-induced phosphatase 1 (Wip1) has been studied extensively in the context of cancer and the regulation of different types of stem cells, but the role of Wip1 in cardiac adaptation to MI is unknown. We investigated the significance of Wip1 in a mouse model of MI. METHODS: The study began in June 2014 and was completed in July 2016. We compared Wip1-knockout (Wip1-KO) mice and wild-type (WT) mice to determine changes in cardiac function and survival in response to MI. The heart weight/body weight (HW/BW) ratio and cardiac function were measured before MI. Mouse MI was established by ligating the left anterior descending (LAD) coronary artery under 1.5% isoflurane anesthesia. After MI, survival of the mice was observed for 4 weeks. Cardiac function was examined by echocardiography. The HW/BW ratio was analyzed, and cardiac hypertrophy was measured by wheat germ agglutinin staining. Hematoxylin and eosin (H&E) staining was used to determine the infarct size. Gene expression of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) was assessed by quantitative real-time polymerase chain reaction (qPCR), and the levels of signal transducers and activators of transcription 3 (stat3) and phosphor-stat3 (p-stat3) were also analyzed by Western blotting. Kaplan-Meier survival analysis, log-rank test, unpaired t-test, and one-way analysis of variance (ANOVA) were used for statistical analyses. RESULTS: Wip1-KO mice had a marginally increased HW/BW ratio and slightly impaired cardiac function before LAD ligation. After MI, Wip1-deficient mice exhibited increased mortality (57.14% vs. 29.17%; n = 24 [WT], n = 35 [Wip1-KO], P< 0.05), increased cardiac hypertrophy (HW/BW ratio: 7 days: 7.25 ± 0.36 vs. 5.84 ± 0.18, n = 10, P< 0.01, and 4 weeks: 6.05 ± 0.17 vs. 5.87 ± 0.24, n = 10, P > 0.05; cross-sectional area: 7 days: 311.80 ± 8.29 vs. 268.90 ± 11.15, n = 6, P< 0.05, and 4 weeks: 308.80 ± 11.26 vs. 317.00 ± 13.55, n = 6, P > 0.05), and reduced cardiac function (ejection fraction: 7 days: 29.37 ± 1.38 vs. 34.72 ± 1.81, P< 0.05, and 4 weeks: 19.06 ± 2.07 vs. 26.37 ± 2.95, P< 0.05; fractional shortening: 7 days: 13.72 ± 0.71 vs. 16.50 ± 0.94, P< 0.05, and 4 weeks: 8.79 ± 1.00 vs. 12.48 ± 1.48, P< 0.05; n = 10 [WT], n = 15 [Wip1-KO]). H&E staining revealed a larger infarct size in Wip1-KO mice than in WT mice (34.79% ± 2.44% vs. 19.55% ± 1.48%, n = 6, P< 0.01). The expression of IL-6 and p-stat3 was downregulated in Wip1-KO mice (IL-6: 1.71 ± 0.27 vs. 4.46 ± 0.79, n = 6, P< 0.01; and p-stat3/stat3: 1.15 ± 0.15 vs. 1.97 ± 0.23, n = 6, P< 0.05). CONCLUSION: The results suggest that Wip1 could protect the heart from MI-induced ischemic injury.